One in every 8 American women develops breast cancer at some point in their lifetime. It is estimated that more than 225,000 new cases of breast cancer occur among American women each year. Breast Conserving Therapy (BCT), defined as excision of the primary tumor and adjacent breast tissue followed by radiation therapy of the breast and/or regional lymph nodes, has been widely accepted as a treatment option for most women with clinical Stage I or II invasive breast cancer. Among the various treatment mechanisms, partial Irradiation treatment through the clever use of megavoltage external beams (called partial breast irradiation (PBI) in this proposal) is a less invasive more focused treatment. It uses a treatment planning CT scan and combines multiple radiation treatment fields to deliver precise doses of radiation externally to the lumpectomy cavity. The major technical challenge for a successful PBI treatment is the precise delivery of radiation dose to the subsurface target volume. Inaccurate localization of the target volume could result in PBI treatment failure due to recurrence caused by geometric miss of the tumor, and/or unacceptable toxicity caused by daily irradiating normal tissue at a high fractional dose. The primary objective of this SBIR program is to develop a novel, three-dimensional (3D), image-guided, adaptive therapy (3D IGAT) technique to improve the precision of radiation delivery during the procedure of Partial Breast Irradiation (PBI) treatment. We propose to develop a novel approach of patient repositioning and error correction based on accurate registration between the treatment-planning computed tomography (CT) scan and the 3D surface profiles of a patient's breast acquired during the treatment. Since 3D surface images can be acquired in real-time and will cause no additional irradiation, the proposed repositioning approach provides an elegant way to solve the two difficulties of the traditional laser line based alignment system. One is accurate localization of the lumpectomy field for dose delivery, and the other is accurate and fast patient repositioning for return visits. The major advantages of this novel technique include the following: 3D surface images. The research results of this SBIR project will lead directly to a new generation of commercial products for accurate and adaptive therapy systems in radiotherapy field. The research results of this SBIR project will lead directly to a new generation of commercial products for adaptive therapy systems in radiotherapy field. With over 2,000 radiation treatment machines in the US and many more worldwide, the market for a clinically acceptable 3D-Camera-based adaptive therapy system is significant.